4区 · 医学
Article
作者: Tarver, James E. ; Finch, Rick ; Fu, Qinghong ; Tari, Leslie W. ; Taylor, Jerry A. ; Keyes, Philip E. ; Hoffman, Isaac ; Wilson, Alan G. E. ; Nouraldeen, Amr ; Swanson, Ronald V. ; Healy, Jason P. ; Stouch, Terry R. ; Shen, Min ; Liu, Qingyun ; Hunter, Michael ; Jessop, Theodore C. ; Yu, Xuan-Chuan ; Augeri, David J. ; Xu, Amy ; David Kimball, S. ; Miranda, Maricar ; Carson, Kenneth G. ; Oravecz, Tamas ; Carlsen, Marianne ; Swaffield, Jonathan C. ; Heim-Riether, Alexander ; Jhaver, Kanchan ; Anderson, Steve ; DiGeorge Foushee, Ann Marie
A series of deoxycytidine kinase inhibitors was simultaneously optimized for potency and PK properties. A co-crystal structure then allowed merging this series with a high throughput screening hit to afford a highly potent, selective and orally bioavailable inhibitor, compound 10. This compound showed dose dependent inhibition of deoxycytidine kinase in vivo.